Imaginative elaboration in agenesis of the corpus callosum: topic modeling and perplexity.

OBJECTIVE: Previous studies have found deficits in imaginative elaboration and social inference to be associated with agenesis of the corpus callosum (ACC; Renteria-Vasquez et al., 2022; Turk et al., 2009). In the current study, Thematic Apperception Test (TAT) responses from a neurotypical control group and a group of individuals with ACC were used to further study the capacity for imaginative elaboration and story coherence. METHOD: Topic modeling was employed utilizing Latent Diritchlet Allocation to characterize the narrative responses to the pictures used in the TAT. A measure of the difference between models (perplexity) was used to compare the topics of the responses of individual participants to the common core model derived from the responses of the control group. Story coherence was tested using sentence-to-sentence Latent Semantic Analysis. RESULTS: Group differences in perplexity were statistically significant overall, and for each card individually (p < .001). There were no differences between the groups in story coherence. CONCLUSIONS: TAT narratives from persons with ACC were normally coherent, but more conventional (i.e., more similar to the core text) compared to those of neurotypical controls. Individuals with ACC can make conventional social inferences about socially ambiguous stimuli, but are restricted in their imaginative elaborations, resulting in less topical variability (lower perplexity values) compared to neurotypical controls.

Comprehensive Social Trait Judgments From Faces in Autism Spectrum Disorder.

Processing social information from faces is difficult for individuals with autism spectrum disorder (ASD). However, it remains unclear whether individuals with ASD make high-level social trait judgments from faces in the same way as neurotypical individuals. Here, we comprehensively addressed this question using naturalistic face images and representatively sampled traits. Despite similar underlying dimensional structures across traits, online adult participants with self-reported ASD showed different judgments and reduced specificity within each trait compared with neurotypical individuals. Deep neural networks revealed that these group differences were driven by specific types of faces and differential utilization of features within a face. Our results were replicated in well-characterized in-lab participants and partially generalized to more controlled face images (a preregistered study). By investigating social trait judgments in a broader population, including individuals with neurodevelopmental variations, we found important theoretical implications for the fundamental dimensions, variations, and potential behavioral consequences of social cognition.

Posttraumatic stress disorder symptom trajectories in a 16-month COVID-19 pandemic period.

COVID-19 pandemic presents an unheralded opportunity to better understand trajectories of posttraumatic stress disorder (PTSD) symptoms across a prolonged period of social disruption and stress. We tracked PTSD symptoms among trauma-exposed individuals in the United States and sought to identify population-based variability in PTSD symptom trajectories and understand what, if any, early pandemic experiences predicted membership in one trajectory versus others. As part of a longitudinal study of U.S. residents during the pandemic, participants who reported at least one potentially traumatic experience in their lifetime (N = 1,206) at Wave 1 (April 2020) were included in the current study. PTSD symptoms were assessed using the PCL-5 at four time points extending to July 2021. Latent growth mixture modeling was used to identify heterogeneous symptom trajectories. Trajectory membership was regressed on experiences from the early stage of the pandemic as measured using the Epidemic-Pandemic Impacts Inventory in a model that controlled for variables with documented associations to PTSD trajectories, including age, sex, income, and trauma history. Four trajectories were identified, categorized as resilient (73.0%), recurring (13.3%), recovering (8.3%), and chronic (5.5%). Emotional and physical health problems and positive changes associated with the early phase of the pandemic were each significant predictors of trajectory membership over and above all other variables in the model. Predictors primarily differentiated the resilient trajectory from each of the other three trajectories. Distinct PTSD symptom trajectories during the COVID-19 pandemic suggest a need for targeted efforts to help individuals at most risk for ongoing distress.

Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe.

OBJECTIVE: Impaired memory is a common comorbidity of refractory temporal lobe epilepsy (TLE) and often perceived by patients as more problematic than the seizures themselves. The objective of this study is to understand what the relationship of these behavioral impairments is to the underlying pathophysiology, as there are currently no treatments for these deficits, and it remains unknown what circuits are affected. METHODS: We recorded single neurons in the medial temporal lobes (MTLs) of 62 patients (37 with refractory TLE) who performed a visual recognition memory task to characterize the relationship between behavior, tuning, and anatomical location of memory selective and visually selective neurons. RESULTS: Subjects with a seizure onset zone (SOZ) in the right but not left MTL demonstrated impaired ability to recollect as indicated by the degree of asymmetry of the receiver operating characteristic curve. Of the 1973 recorded neurons, 159 were memory selective (MS) and 366 were visually selective (VS) category cells. The responses of MS neurons located within right but not left MTL SOZs were impaired during high-confidence retrieval trials, mirroring the behavioral deficit seen both in our task and in standardized neuropsychological tests. In contrast, responses of VS neurons were unimpaired in both left and right MTL SOZs. Our findings show that neuronal dysfunction within SOZs in the MTL was specific to a functional cell type and behavior, whereas other cell types respond normally even within the SOZ. We show behavioral metrics that detect right MTL SOZ-related deficits and identify a neuronal correlate of this impairment. SIGNIFICANCE: Together, these findings show that single-cell responses can be used to assess the causal effects of local circuit disruption by an SOZ in the MTL, and establish a neural correlate of cognitive impairment due to epilepsy that can be used as a biomarker to assess the efficacy of novel treatments.

Everyday Executive Function and Self-Awareness in Agenesis of the Corpus Callosum.

OBJECTIVE: Agenesis of the corpus callosum (AgCC) is associated with a range of cognitive deficits, including mild to moderate problems in higher order executive functions evident in neuropsychological assessments. Previous research has also suggested a lack of self-awareness in persons with AgCC. METHOD: We investigated daily executive functioning and self-awareness in 36 individuals with AgCC by analyzing self-ratings on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), as well as ratings on the same instrument from close relatives. Discrepancies between self- and informant-ratings were compared to the normative sample and exploratory analyses examined possible moderating effects of participant and informant characteristics. RESULTS: Significant deficiencies were found in the Behavioral Regulation and Metacognitive indices for both the self and informant results, with elevated frequency of metacognition scores in the borderline to clinical range. Informants also endorsed elevated frequency of borderline to clinically significant behavioral regulation scores. The proportion of AgCC participants whose self-ratings indicated less metacognitive impairment than informant-ratings was greater than in the normative sample. Self-ratings of behavioral regulation impairment decreased with age and informant-ratings of metacognition were higher in males than females. CONCLUSIONS: These findings provide evidence that individuals with AgCC experience mild to moderate executive functioning problems in everyday behavior which are observed by others. Results also suggest a lack of self-understanding or insight into the severity of these problems in the individuals with AgCC, particularly with respect to their metacognitive functioning.

Anthropomorphizing without Social Cues Requires the Basolateral Amygdala.

Anthropomorphism, the attribution of distinctively human mental characteristics to nonhuman animals and objects, illustrates the human propensity for extending social cognition beyond typical social targets. Yet, its processing components remain challenging to study because they are typically all engaged simultaneously. Across one pilot study and one focal study, we tested three rare people with basolateral amygdala lesions to dissociate two specific processing components: those triggered by attention to social cues (e.g., seeing a face) and those triggered by endogenous semantic knowledge (e.g., imbuing a machine with animacy). A pilot study demonstrated that, like neurologically intact control group participants, the three amygdala-damaged participants produced anthropomorphic descriptions for highly socially salient stimuli but not for stimuli lacking clear social cues. A focal study found that the three amygdala participants could anthropomorphize animate and living entities normally, but anthropomorphized inanimate stimuli less than control participants. Our findings suggest that the amygdala contributes to how we anthropomorphize stimuli that are not explicitly social.

The Neuropsychological Syndrome of Agenesis of the Corpus Callosum.

BACKGROUND: Agenesis of the corpus callosum (AgCC) involves congenital absence of all or part of the corpus callosum. Because the disorder can only be firmly diagnosed via neuroradiology, it has a short research history, and only recently has the cognitive syndrome become clear. PURPOSE: Our purpose is to review the primary deficits in AgCC that constitute the core syndrome. CONCLUSIONS: The cores syndrome includes: (1) reduced interhemispheric transfer of sensory-motor information; (2) reduced cognitive processing speed; and (3) deficits in complex reasoning and novel problem-solving. These domains do not appear to reflect different neuroanatomical abnormalities, but rather different domains of expression of reduced interhemispheric communication from callosal absence. IMPLICATIONS: These core deficits are expressed across various domains of cognitive, behavioral, and social functioning. The impact of these deficits varies across development and may be moderated by individual factors such as co-occurrence of other neurodevelopmental conditions, general intellectual capacity, and environmental support. (JINS, 2019, 25, 324-330).

Agenesis of the corpus callosum and autism: a comprehensive comparison.

The corpus callosum, with its ∼200 million axons, remains enigmatic in its contribution to cognition and behaviour. Agenesis of the corpus callosum is a congenital condition in which the corpus callosum fails to develop; such individuals exhibit localized deficits in non-literal language comprehension, humour, theory of mind and social reasoning. These findings together with parent reports suggest that behavioural and cognitive impairments in subjects with callosal agenesis may overlap with the profile of autism spectrum disorders, particularly with respect to impairments in social interaction and communication. To provide a comprehensive test of this hypothesis, we directly compared a group of 26 adults with callosal agenesis to a group of 28 adults with a diagnosis of autism spectrum disorder but no neurological abnormality. All participants had full-scale intelligence quotient scores >78 and groups were matched on age, handedness, and gender ratio. Using the Autism Diagnostic Observation Schedule together with current clinical presentation to assess autistic symptomatology, we found that 8/26 (about a third) of agenesis subjects presented with autism. However, more formal diagnosis additionally involving recollective parent-report measures regarding childhood behaviour showed that only 3/22 met complete formal criteria for an autism spectrum disorder (parent reports were unavailable for four subjects). We found no relationship between intelligence quotient and autism symptomatology in callosal agenesis, nor evidence that the presence of any residual corpus callosum differentiated those who exhibited current autism spectrum symptoms from those who did not. Relative to the autism spectrum comparison group, parent ratings of childhood behaviour indicated children with agenesis were less likely to meet diagnostic criteria for autism, even for those who met autism spectrum criteria as adults, and even though there was no group difference in parent report of current behaviours. The findings suggest two broad conclusions. First, they support the hypothesis that congenital disruption of the corpus callosum constitutes a major risk factor for developing autism. Second, they quantify specific features that distinguish autistic behaviour associated with callosal agenesis from autism more generally. Taken together, these two findings also leverage specific questions for future investigation: what are the distal causes (genetic and environmental) determining both callosal agenesis and its autistic features, and what are the proximal mechanisms by which absence of the callosum might generate autistic symptomatology?

Largely typical patterns of resting-state functional connectivity in high-functioning adults with autism.

A leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, yet the majority of studies report effects that are either very weak, inconsistent across studies, or explain results incompletely. Here we apply multiple analytical approaches to resting-state BOLD-fMRI data at the whole-brain level. Neurotypical and high-functioning adults with autism displayed very similar patterns and strengths of resting-state connectivity. We found only limited evidence in autism for abnormal resting-state connectivity at the regional level and no evidence for altered connectivity at the whole-brain level. Regional abnormalities in functional connectivity in autism spectrum disorder were primarily in the frontal and temporal cortices. Within these regions, functional connectivity with other brain regions was almost exclusively lower in the autism group. Further examination showed that even small amounts of head motion during scanning have large effects on functional connectivity measures and must be controlled carefully. Consequently, we suggest caution in the interpretation of apparent positive findings until all possible confounding effects can be ruled out. Additionally, we do not rule out the possibility that abnormal connectivity in autism is evident at the microstructural synaptic level, which may not be reflected sensitively in hemodynamic changes measured with BOLD-fMRI.

Lesion mapping of cognitive control and value-based decision making in the prefrontal cortex.

A considerable body of previous research on the prefrontal cortex (PFC) has helped characterize the regional specificity of various cognitive functions, such as cognitive control and decision making. Here we provide definitive findings on this topic, using a neuropsychological approach that takes advantage of a unique dataset accrued over several decades. We applied voxel-based lesion-symptom mapping in 344 individuals with focal lesions (165 involving the PFC) who had been tested on a comprehensive battery of neuropsychological tasks. Two distinct functional-anatomical networks were revealed within the PFC: one associated with cognitive control (response inhibition, conflict monitoring, and switching), which included the dorsolateral prefrontal cortex and anterior cingulate cortex and a second associated with value-based decision-making, which included the orbitofrontal, ventromedial, and frontopolar cortex. Furthermore, cognitive control tasks shared a common performance factor related to set shifting that was linked to the rostral anterior cingulate cortex. By contrast, regions in the ventral PFC were required for decision-making. These findings provide detailed causal evidence for a remarkable functional-anatomical specificity in the human PFC.

Exploiting ChatGPT for Diagnosing Autism-Associated Language Disorders and Identifying Distinct Features.

Diagnosing language disorders associated with autism is a complex and nuanced challenge, often hindered by the subjective nature and variability of traditional assessment methods. Traditional diagnostic methods not only require intensive human effort but also often result in delayed interventions due to their lack of speed and specificity. In this study, we explored the application of ChatGPT, a state-of-the-art large language model, to overcome these obstacles by enhancing diagnostic accuracy and profiling specific linguistic features indicative of autism. Leveraging ChatGPT's advanced natural language processing capabilities, this research aims to streamline and refine the diagnostic process. Specifically, we compared ChatGPT's performance with that of conventional supervised learning models, including BERT, a model acclaimed for its effectiveness in various natural language processing tasks. We showed that ChatGPT substantially outperformed these models, achieving over 13% improvement in both accuracy and F1-score in a zero-shot learning configuration. This marked enhancement highlights the model's potential as a superior tool for neurological diagnostics. Additionally, we identified ten distinct features of autism-associated language disorders that vary significantly across different experimental scenarios. These features, which included echolalia, pronoun reversal, and atypical language usage, were crucial for accurately diagnosing ASD and customizing treatment plans. Together, our findings advocate for adopting sophisticated AI tools like ChatGPT in clinical settings to assess and diagnose developmental disorders. Our approach not only promises greater diagnostic precision but also aligns with the goals of personalized medicine, potentially transforming the evaluation landscape for autism and similar neurological conditions.

Smartphone-based gaze estimation for in-home autism research.

Atypical gaze patterns are a promising biomarker of autism spectrum disorder. To measure gaze accurately, however, it typically requires highly controlled studies in the laboratory using specialized equipment that is often expensive, thereby limiting the scalability of these approaches. Here we test whether a recently developed smartphone-based gaze estimation method could overcome such limitations and take advantage of the ubiquity of smartphones. As a proof-of-principle, we measured gaze while a small sample of well-assessed autistic participants and controls watched videos on a smartphone, both in the laboratory (with lab personnel) and in remote home settings (alone). We demonstrate that gaze data can be efficiently collected, in-home and longitudinally by participants themselves, with sufficiently high accuracy (gaze estimation error below 1° visual angle on average) for quantitative, feature-based analysis. Using this approach, we show that autistic individuals have reduced gaze time on human faces and longer gaze time on non-social features in the background, thereby reproducing established findings in autism using just smartphones and no additional hardware. Our approach provides a foundation for scaling future research with larger and more representative participant groups at vastly reduced cost, also enabling better inclusion of underserved communities.

Verbal problem-solving in agenesis of the corpus callosum: Analysis using semantic similarity.

OBJECTIVE: Previous studies demonstrated that individuals with agenesis of the corpus callosum (AgCC) experience difficulties in novel and complex problem-solving. The present study investigated verbal problem-solving, deductive reasoning, and semantic inference in AgCC. METHOD: Capacity for semantic inference was tested in 25 individuals with AgCC and normal-range intelligence compared to 29 neurotypical controls. The Word Context Test (WCT) of Delis-Kaplan Executive Function System was used, employing a novel method of analysis (semantic similarity) to detect trial-by-trial progress toward a solution. RESULTS: With respect to the typical WCT scores, persons with AgCC had fewer total consecutive correct responses. In addition, semantic similarity to the correct word was significantly lower overall in persons with AgCC than in controls. CONCLUSION: These findings indicated that individuals with AgCC who have intelligence in the normal range are less able at the WCT taking all trials into account, although they often solve the problem eventually. This outcome is consistent with previous research indicating that callosal absence in AgCC results in a restricted imagination for possibilities, limiting their problem-solving and inferential capacities. The results also highlight the usefulness of semantic similarity as a means of scoring the WCT. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neural signatures of social inferences predict the number of real-life social contacts and autism severity.

We regularly infer other people's thoughts and feelings from observing their actions, but how this ability contributes to successful social behavior and interactions remains unknown. We show that neural activation patterns during social inferences obtained in the laboratory predict the number of social contacts in the real world, as measured by the social network index, in three neurotypical samples (total n = 126) and one sample of autistic adults (n = 23). We also show that brain patterns during social inference generalize across individuals in these groups. Cross-validated associations between brain activations and social inference localize selectively to the right posterior superior temporal sulcus and were specific for social, but not nonsocial, inference. Activation within this same brain region also predicts autism-like trait scores from questionnaires and autism symptom severity. Thus, neural activations produced while thinking about other people's mental states predict variance in multiple indices of social functioning in the real world.

Dissociable brain structural asymmetry patterns reveal unique phenome-wide profiles.

Broca reported ~150 years ago that particular lesions of the left hemisphere impair speech. Since then, other brain regions have been reported to show lateralized structure and function. Yet, studies of brain asymmetry have limited their focus to pairwise comparisons between homologous regions. Here, we characterized separable whole-brain asymmetry patterns in grey and white matter structure from n = 37,441 UK Biobank participants. By pooling information on left-right shifts underlying whole-brain structure, we deconvolved signatures of brain asymmetry that are spatially distributed rather than locally constrained. Classically asymmetric regions turned out to belong to more than one asymmetry pattern. Instead of a single dominant signature, we discovered complementary asymmetry patterns that contributed similarly to whole-brain asymmetry at the population level. These asymmetry patterns were associated with unique collections of phenotypes, ranging from early lifestyle factors to demographic status to mental health indicators.

COVID-Dynamic: A large-scale longitudinal study of socioemotional and behavioral change across the pandemic.

The COVID-19 pandemic has caused enormous societal upheaval globally. In the US, beyond the devastating toll on life and health, it triggered an economic shock unseen since the great depression and laid bare preexisting societal inequities. The full impacts of these personal, social, economic, and public-health challenges will not be known for years. To minimize societal costs and ensure future preparedness, it is critical to record the psychological and social experiences of individuals during such periods of high societal volatility. Here, we introduce, describe, and assess the COVID-Dynamic dataset, a within-participant longitudinal study conducted from April 2020 through January 2021, that captures the COVID-19 pandemic experiences of >1000 US residents. Each of 16 timepoints combines standard psychological assessments with novel surveys of emotion, social/political/moral attitudes, COVID-19-related behaviors, tasks assessing implicit attitudes and social decision-making, and external data to contextualize participants' responses. This dataset is a resource for researchers interested in COVID-19-specific questions and basic psychological phenomena, as well as clinicians and policy-makers looking to mitigate the effects of future calamities.

Alcohol, cannabis, and nicotine use have distinct associations with COVID-19 pandemic-related experiences: An exploratory Bayesian network analysis across two timepoints.

BACKGROUND: Substance use trends during the COVID-19 pandemic have been extensively documented. However, relatively less is known about the associations between pandemic-related experiences and substance use. METHOD: In July 2020 and January 2021, a broad U.S. community sample (N = 1123) completed online assessments of past month alcohol, cannabis, and nicotine use and the 92-item Epidemic-Pandemic Impacts Inventory, a multidimensional measure of pandemic-related experiences. We examined links between substance use frequency, and pandemic impact on emotional, physical, economic, and other key domains, using Bayesian Gaussian graphical networks in which edges represent significant associations between variables (referred to as nodes). Bayesian network comparison approaches were used to assess the evidence of stability (or change) in associations between the two timepoints. RESULTS: After controlling for all other nodes in the network, multiple significant edges connecting substance use nodes and pandemic-experience nodes were observed across both time points, including positive- (r range 0.07-0.23) and negative-associations (r range -0.25 to -0.11). Alcohol was positively associated with social and emotional pandemic impacts and negatively associated with economic impacts. Nicotine was positively associated with economic impact and negatively associated with social impact. Cannabis was positively associated with emotional impact. Network comparison suggested these associations were stable across the two timepoints. CONCLUSION: Alcohol, nicotine, and cannabis use had unique associations to a few specific domains among a broad range of pandemic-related experiences. Given the cross-sectional nature of these analyses with observational data, further investigation is needed to identify potential causal links.

Intact bilateral resting-state networks in the absence of the corpus callosum.

Temporal correlations between different brain regions in the resting-state BOLD signal are thought to reflect intrinsic functional brain connectivity (Biswal et al., 1995; Greicius et al., 2003; Fox et al., 2007). The functional networks identified are typically bilaterally distributed across the cerebral hemispheres, show similarity to known white matter connections (Greicius et al., 2009), and are seen even in anesthetized monkeys (Vincent et al., 2007). Yet it remains unclear how they arise. Here we tested two distinct possibilities: (1) functional networks arise largely from structural connectivity constraints, and generally require direct interactions between functionally coupled regions mediated by white-matter tracts; and (2) functional networks emerge flexibly with the development of normal cognition and behavior and can be realized in multiple structural architectures. We conducted resting-state fMRI in eight adult humans with complete agenesis of the corpus callosum (AgCC) and normal intelligence, and compared their data to those from eight healthy matched controls. We performed three main analyses: anatomical region-of-interest-based correlations to test homotopic functional connectivity, independent component analysis (ICA) to reveal functional networks with a data-driven approach, and ICA-based interhemispheric correlation analysis. Both groups showed equivalently strong homotopic BOLD correlation. Surprisingly, almost all of the group-level independent components identified in controls were observed in AgCC and were predominantly bilaterally symmetric. The results argue that a normal complement of resting-state networks and intact functional coupling between the hemispheres can emerge in the absence of the corpus callosum, favoring the second over the first possibility listed above.

Processing speed delays contribute to executive function deficits in individuals with agenesis of the corpus callosum.

Corpus callosum malformation and dysfunction are increasingly recognized causes of cognitive and behavioral disability. Individuals with agenesis of the corpus callosum (AgCC) offer unique insights regarding the cognitive skills that depend specifically upon callosal connectivity. We examined the impact of AgCC on cognitive inhibition, flexibility, and processing speed using the Color-Word Interference Test (CWIT) and Trail Making Test (TMT) from the Delis-Kaplan Executive Function System. We compared 36 individuals with AgCC and IQs within the normal range to 56 matched controls. The AgCC cohort was impaired on timed measures of inhibition and flexibility; however, group differences on CWIT Inhibition, CWIT Inhibition/Switching and TMT Number-Letter Switching appear to be largely explained by slow performance in basic operations such as color naming and letter sequencing. On CWIT Inhibition/Switching, the AgCC group was found to commit significantly more errors which suggests that slow performance is not secondary to a cautious strategy. Therefore, while individuals with agenesis of the corpus callosum show real deficits on tasks of executive function, this impairment appears to be primarily a consequence of slow cognitive processing. Additional studies are needed to investigate the impact of AgCC on other aspects of higher order cortical function.

Social Inferences in Agenesis of the Corpus Callosum and Autism: Semantic Analysis and Topic Modeling.

Impoverished capacity for social inference is one of several symptoms that are common to both agenesis of the corpus callosum (AgCC) and Autism Spectrum Disorder (ASD). This research compared the ability of 14 adults with AgCC, 13 high-functioning adults with ASD and 14 neurotypical controls to accurately attribute social meaning to the interactions of animated triangles. Descriptions of the animations were analyzed in three ways: subjective ratings, Linguistic Inquiry and Word Count, and topic modeling (Latent Dirichlet Allocation). Although subjective ratings indicated that all groups made similar inferences from the animations, the index of perplexity (atypicality of topic) generated from topic modeling revealed that inferences from individuals with AgCC or ASD displayed significantly less social imagination than those of controls.